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Results for “Enhancer mapping”

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PubMed1999

Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B).

We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa25-44 MAP compared with mice immunized with the 25-44 monomer. Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25-44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa287-301 determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa287-301 peptide. However, immunization with the multivalent mLa287-301 peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa287-301 peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence.

Amino Acid Sequence↗

PubMed1994

Mapping and characterization of a retinoic acid-responsive enhancer of midkine, a novel heparin-binding growth/differentiation factor with neurotrophic activity.

MK is a gene that is activated by retinoic acid in embryonal carcinoma (EC) cells and is expressed temporarily during the mid-gestation period of mouse embryogenesis. Midkine, the product of the gene is a novel heparin-binding growth/differentiation factor with neurite outgrowth and neurotrophic activities. The regulatory DNA element in the retinoic acid-induced expression of the MK gene has been investigated. The 1.9 kb 5'-flanking region of the MK gene can mediate retinoic acid-responsive gene expression in F9 and HM-1 EC cells. Analysis of this region by deletion mutagenesis in F9 EC cells shows that there is a retinoic acid-responsive enhancer (designated as REM1) around 900 bp upstream from the transcription start site. This enhancer is composed of two sequence elements, which are located between -1006 and -895 and between -901 and -794. The core element of the upstream region (-971 to -955), whose deletion abolished the retinoic acid responsiveness, contained a sequence highly homologous to a binding site for retinoic acid receptors. Binding of a retinoic acid receptor heterodimer to this core element was verified by gel shift assay. Thus, retinoic acid and the receptor complex can directly induce the expression of a growth/differentiation factor gene.

Animals↗

PubMed1998

Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation.

The immunofluorescence localization of alphaB-crystallin in U373 MG human glioma cells with an antibody specific for alphaB-crystallin that had been phosphorylated at Ser-45 revealed an intense staining of cells in the mitotic phase of the cell cycle. Phosphorylated forms of alphaB-crystallin in mitotic cells were detected in all cell lines examined and in tissue sections of mouse embryos. Increases in the levels of alphaB-crystallin that had been phosphorylated at Ser-45 and Ser-19, but not at Ser-59, were detected biochemically by isoelectric focusing or SDS-polyacrylamide gel electrophoresis and a subsequent Western blot analysis of extracts of cells collected at the mitotic phase. When we estimated the phosphorylation activity specific for alphaB-crystallin in extracts of mitotic U373 MG cells, using the amino-terminal 72-amino acid peptide derived from unphosphorylated alphaB2-crystallin as the substrate, we found that the activities responsible for the phosphorylation of Ser-45 and Ser-19 were markedly enhanced but that the activity responsible for the phosphorylation of Ser-59 was suppressed. The protein kinases responsible for the phosphorylation of Ser-45 and Ser-59 in the amino-terminal 72-amino acid peptide were partially purified from extracts of cells that had been stimulated by exposure to H2O2 in the presence of calyculin A. The activities responsible for the phosphorylation of Ser-45 and Ser-59 were eluted separately from a column of Superdex 200 at fractions corresponding to about 40 and 60 kDa, respectively, while the kinase for Ser-19 was unstable. p44/42 mitogen-activated protein (MAP) kinase and MAP kinase-activated protein (MAPKAP) kinase-2 were concentrated in the Ser-45 kinase fraction and Ser-59 kinase fraction, respectively. Recombinant human p44 MAP kinase and MAPKAP kinase-2 purified from rabbit muscle selectively phosphorylated Ser-45 and -59, respectively. The Ser-45 kinase fraction and Ser-59 kinase fraction phosphorylated myelin basic protein and hsp27, respectively. These results suggest that the phosphorylations of Ser-45 and Ser-59 in alphaB-crystallin are catalyzed by p44/42 MAP kinase and MAPKAP kinase-2, respectively, in cells and that the phosphorylation of Ser-45 by p44/42 MAP kinase is enhanced while the phosphorylation of Ser-59 by MAPKAP kinase-2 is suppressed during cell division.

Animals↗

PubMed2001

Dopexamine hydrochloride does not modify hemodynamic response or tissue oxygenation or gut permeability during abdominal aortic surgery.

PURPOSE: To assess the effects of intraoperative infusion of dopexamine (a DA-1 and B2 adrenoreceptor agonist) on hemodynamic function, tissue oxygen delivery and consumption, splanchnic perfusion and gut permeability following aortic cross- clamp and release. METHODS: In a randomised double blind controlled trial 24 patients scheduled for elective infrarenal abdominal aortic aneurysm repair were studied in two centres and were assigned to one of two treatment groups. Group I received a dopexamine infusion starting at 0.5 microg x kg(-1) x min(-1) increased to 2 microg x kg(-1) x min(-1) maintaining a stable heart rate; Group II received a placebo infusion titrated in the same volumes following induction of anesthesia. Measured and derived hemodynamic data, tissue oxygen delivery and extraction and gut permeability were recorded at set time points throughout the procedure. RESULTS: Dopexamine infusion (0.5 -2 microg x kg x min(-1)) was associated with enhanced hemodynamic function (MAP 65 +/- 5.5 vs 92 +/- 5.7 mm Hg, P = <0.05) only during the period of aortic cross clamping. However, during the most part of infrarenal abdominal aortic surgery, dopexamine did not reduce systemic vascular resistance index, mean arterial pressure nor oxygen extraction compared with the control group. The lactulose/ rhamnose permeation ratio was elevated above normal in both groups (0.22 and 0.29 in groups I and II respectively). CONCLUSIONS: Dopexamine infusion (0.5 -2 microg x kg(-1) x min(-1)) did not enhance hemodynamic function and tissue oxygenation values during elective infrarenal abdominal aortic aneurysm repair.

Aged↗

PubMed1998

Signal transduction mechanisms involved in angiotensin-(1-7)-stimulated arachidonic acid release and prostanoid synthesis in rabbit aortic smooth muscle cells.

This study investigated the signal transduction mechanisms of angiotensin-(1-7) [Ang-(1-7)]- and Ang II-stimulated arachidonic acid (AA) release for prostaglandin (PG) production in rabbit aortic vascular smooth muscle cells. Ang II and Ang-(1-7) enhanced AA release in cells prelabeled with [3H]AA. However, 6-keto-PGF1 alpha synthesis produced by Ang II was much less than that caused by Ang-(1-7). In the presence of the lipoxygenase inhibitor baicalein, Ang II enhanced production of 6-keto-PGF1 alpha to a greater degree than Ang-(1-7). Angiotensin type (AT)1 receptor antagonist DUP-753 inhibited only Ang II-induced [3H]AA release, whereas the AT2 receptor antagonist PD-123319 inhibited both Ang II- and Ang-(1-7)-induced [3H]AA release. Ang-(1-7), receptor antagonist D-Ala7-Ang-(1-7) inhibited the effect of Ang-(1-7), but not of Ang II. In cells transiently transfected with cytosolic phospholipase A2 (cPLA2), mitogen-activated protein (MAP) kinase or Ca(++)-/cal-modulin-dependent protein (CAM) kinase II antisense oligonucleotides, Ang-(1-7)- and Ang II-induced [3H]AA release was attenuated. The CaM kinase II inhibitor KN-93 and the MAP kinase kinase inhibitor PD-98059 attenuated both Ang-(1-7)- and Ang II-induced cPLA2 activity and [3H]AA release. Ang-(1-7) and Ang II also increased CaM kinase II and MAP kinase activities. Although KN-93 attenuated MAP kinase activity, PD-98059 did not affect CaM kinase II activity. Both Ang II and Ang-(1-7) caused translocation of cytosolic PLA2 to the nuclear envelope. These data show that Ang-(1-7) and Ang II stimulate AA release and prostacyclin synthesis via activation of distinct types of AT receptors. Both peptides appear to stimulate CaM kinase II, which in turn, via MAP kinase activation, enhances cPLA2 activity and release of AA for PG synthesis.

Angiotensin I↗

PubMed2005

A review of geographic information system and remote sensing with applications to the epidemiology and control of schistosomiasis in China.

Geographic information system (GIS) and remote sensing (RS) technologies offer new opportunities for rapid assessment of endemic areas, provision of reliable estimates of populations at risk, prediction of disease distributions in areas that lack baseline data and are difficult to access, and guidance of intervention strategies, so that scarce resources can be allocated in a cost-effective manner. Here, we focus on the epidemiology and control of schistosomiasis in China and review GIS and RS applications to date. These include mapping prevalence and intensity data of Schistosoma japonicum at a large scale, and identifying and predicting suitable habitats for Oncomelania hupensis, the intermediate host snail of S. japonicum, at a small scale. Other prominent applications have been the prediction of infection risk due to ecological transformations, particularly those induced by floods and water resource developments, and the potential impact of climate change. We also discuss the limitations of the previous work, and outline potential new applications of GIS and RS techniques, namely quantitative GIS, WebGIS, and utilization of emerging satellite information, as they hold promise to further enhance infection risk mapping and disease prediction. Finally, we stress current research needs to overcome some of the remaining challenges of GIS and RS applications for schistosomiasis, so that further and sustained progress can be made to control this disease in China and elsewhere.

Animals↗

PubMed2006

Simultaneous cardiac and respiratory synchronization in oxygen-enhanced magnetic resonance imaging of the lung using a pneumotachograph for respiratory monitoring.

OBJECTIVES: We sought to evaluate an optimized method for oxygen-enhanced magnetic resonance imaging of the lung, using electrocardiogram-trigger and a pneumotachograph for simultaneous cardiac and respiratory synchronization. MATERIALS AND METHODS: Five series of IR-SSFSE images (echo time = 28.2 milliseconds; inversion time = 1,200 milliseconds) were obtained in 6 volunteers during the ventilation-paradigm room-air/oxygen/room-air: series 1, respiratory-triggered; series 2, cardiac-triggered; series 3, cardiac-triggered and respiratory-synchronized using the signal of the pneumatic belt; series 4, cardiac-triggered and respiratory-synchronized using the external signal of the pneumotachograph; and series 5, not cardiac-triggered and respiratory-synchronized using the signal of the pneumotachograph. Standard deviations of the lung (SI(var)) and diaphragm mismatch (DM) were measured. The relative SI change (DeltaSI) was computed from room-air and oxygen-enhanced images. Parametric maps were obtained from cross-correlation analysis of the ventilation paradigm. Mean correlation coefficients (cc) and the percentage of activated pixels over the lung (Act%) were calculated from these maps. All 5 parameters were compared among the 5 series (Friedman-analysis of variance, Dunn's posthoc test). RESULTS: In series 4, DM and SI(var) were significantly lower than in respiratory and cardiac-triggered series (DM = 4.7 vs. 14.3 and 18.4; SI(var) = 4.9 vs. 10 and 11). In the same series cc and Act% also were significantly higher than in series 1 and 2 (cc = 0.86 vs. 0.7 and 0.6; Act% = 71.3 vs. 44.7 and 41.2). DeltaSI was not significantly different among all series. CONCLUSIONS: Effective respiratory and cardiac synchronization can be achieved in oxygen-enhanced magnetic resonance imaging of the lung, using a pneumotachograph for real-time targeting of end-expiration.

Adult↗

PubMed1991

iciA, an Escherichia coli gene encoding a specific inhibitor of chromosomal initiation of replication in vitro.

The gene encoding the protein that binds the three 13-mers in the origin (oriC) of Escherichia coli to block initiation of replication in vitro has been cloned, sequenced, and overexpressed. The gene possesses an open reading frame for 297 amino acids (mass of 33,471 Da). The protein has a motif for DNA-binding (helix-turn-helix) and has homology to a diverse set of prokaryotic regulatory proteins, known as the LysR family. The protein, previously referred to as the 33-kDa protein, has been named IciA (for inhibitor of chromosome initiation). The iciA gene is at 62.8 min on the chromosomal map. Cells with enhanced levels of the protein grow at a normal rate but generally exhibit a pronounced lag upon transfer to a fresh medium.

Amino Acid Sequence↗

PubMed1998

Regulation of the fibroblast growth factor receptor 3 promoter and intron I enhancer by Sp1 family transcription factors.

Fibroblast growth factor receptor 3 (FGFR3) has a complex spatial and temporal pattern of expression and is essential for the normal development of a diverse set of tissues. Recently, mutations have been identified in FGFR3 that result in constitutive tyrosine kinase activity and cause a number of different human skeletal disorders. To examine the regulatory mechanisms governing FGFR3 expression, the promoter for the FGFR3 gene was identified and characterized. It resides in a CpG island, which encompasses the 5' end of the FGFR3 gene and lacks classical cis-regulatory motifs. As little as 100 base pairs of sequence 5' to the initiation site can confer a 20-40-fold increase in transcriptional activity upon a promoter-less vector. The transcriptional activity of these cis-regulatory sequences is further stimulated by elements found within the first intron. Mapping of the enhancer activity found within intron I identified two purine-rich sequence motifs between +340 and +395. Electrophoretic mobility shift assays demonstrated that sequences within this region bind members of the Sp1 family of transcription factors. In a background lacking Sp1-like activity, we demonstrate that Sp1 can enhance transcription of the minimal promoter (which contains five classical Sp1 sites), whereas both Sp1 and Sp3 can enhance transcription through the elements found in intron I. Although these transcription factors are ubiquitously expressed, we demonstrate that the sequences between -220 and +609 of the FGFR3 gene are sufficient to promote the tissue-specific expression of a reporter gene in transgenic mice.

Animals↗

PubMed1999

c-Raf-mediated inhibition of epidermal growth factor-stimulated cell migration.

Epidermal growth factor stimulates migration of a number of cell types, yet the signaling pathways that regulate epidermal growth factor-stimulated migration are poorly defined. In this report, we employ a transient transfection migration assay to assess the role of components of the Ras-mitogen-activated protein (MAP) kinase signaling pathway in epidermal growth factor-stimulated chemotaxis of rat embryo fibroblasts. Expression of dominant negative Ras blocks epidermal growth factor-mediated chemotaxis, while constitutively active Ras has no effect on chemokinesis or chemotaxis. PD98059 and U0126, inhibitors of MAP kinase kinase (MEK) activity, decreased epidermal growth factor-stimulated migration, while kinase-defective MEK1, an inhibitor of MAP kinase activation, enhanced migration. To understand the paradoxical effects of these molecules on epidermal growth factor-induced migration, we examined the role of c-Raf on migration. Expression of either wild type c-Raf or the catalytic domain of c-Raf effectively inhibited epidermal growth factor-stimulated cell migration. We suggest that, whereas Ras activity is necessary to promote epidermal growth factor-stimulated migration, sustained activation of c-Raf may be important in down-regulating migratory signaling pathways triggered by epidermal growth factor receptor activation. Further, activation of c-Raf upon inhibition of the MEK-MAP kinase pathway may contribute to the inhibition of cell migration observed with pharmacological MEK inhibitors.

Animals↗

PubMed2000

Hierarchical state space partitioning with a network self-organising map for the recognition of ST-T segment changes.

The problem of maximising the performance of ST-T segment automatic recognition for ischaemia detection is a difficult pattern classification problem. The paper proposes the network self-organising map (NetSOM) model as an enhancement to the Kohonen self-organised map (SOM) model. This model is capable of effectively decomposing complex large-scale pattern classification problems into a number of partitions, each of which is more manageable with a local classification device. The NetSOM attempts to generalize the regularization and ordering potential of the basic SOM from the space of vectors to the space of approximating functions. It becomes a device for the ordering of local experts (i.e. independent neural networks) over its lattice of neurons and for their selection and co-ordination. Each local expert is an independent neural network that is trained and activated under the control of the NetSOM. This method is evaluated with examples from the European ST-T database. The first results obtained after the application of NetSOM to ST-T segment change recognition show a significant improvement in the performance compared with that obtained with monolithic approaches, i.e. with single network types. The basic SOM model has attained an average ischaemic beat sensitivity of 73.6% and an average ischaemic beat predictivity of 68.3%. The work reports and discusses the improvements that have been obtained from the implementation of a NetSOM classification system with both multilayer perceptrons and radial basis function (RBF) networks as local experts for the ST-T segment change problem. Specifically, the NetSOM with multilayer perceptrons (radial basis functions) as local experts has improved the results over the basic SOM to an average ischaemic beat sensitivity of 75.9% (77.7%) and an average ischaemic beat predictivity of 72.5% (74.1%).

Electrocardiography↗

PubMed2001

Differential effects of trihexyphenidyl on place preference conditioning and locomotor stimulant activity of cocaine and methamphetamine.

Cocaine produces rewarding and locomotor stimulant effects by increasing extracellular dopamine (DA) levels in the terminal areas of the mesolimbic DA system. Our recent in vitro studies have shown that a muscarinic receptor antagonist, trihexyphenidyl (THP) inhibits the binding of a cocaine analogue to the DA transporter at concentrations that are ineffective in inhibiting 3H-DA uptake, suggesting that THP may attenuate the actions of cocaine selectively. The present study examined whether THP could affect conditioned place preference (CPP) for and locomotor stimulant activity of cocaine and methamphetamine (MAP) in mice. Mice were injected with cocaine (10 mg/kg) or MAP (1 mg/kg) in one compartment of the CPP chamber 4 times every second day. On alternate days the animals received saline in the other compartment of the CPP chamber. Pretreatment with THP was made 10 min before cocaine or MAP injection. The CPP score and locomotor activity were assessed using a novel activity monitor, SCANET. Cocaine and MAP produced CPP for the drug-paired compartment. Pretreatment with THP (0.05-5 mg/kg) had no influence on cocaine-induced CPP at any dose tested. In contrast, MAP-induced CPP was completely antagonized by THP at 5 mg/kg, which produced no CPP by itself. Another muscarinic receptor antagonist, scopolamine (SCP, 3 mg/kg) neither caused CPP by itself nor affected the development of cocaine- or MAP-induced CPP. Both THP and SCP enhanced spontaneous, cocaine- or MAP-induced locomotor activity. Though the present conditioning treatments failed to develop locomotor sensitization to cocaine, THP, but not SCP, acted cooperatively with cocaine to develop locomotor sensitization. The development of locomotor sensitization to MAP was retarded by SCP but was not affected by THP. These results suggest that, contrary to our anticipation, THP has a unique characteristic of specifically counter-acting the rewarding properties of MAP via a non-cholinergic (muscarinic) mechanism.

Animals↗

PubMed2006

Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI.

This magnetic resonance imaging (MRI) study describes mapping of the habenulo-interpeduncular pathway in living mice based on manganese-induced contrast. Six hours after intracerebroventricular microinjection of MnCl2, T1-weighted 3D MRI (2.35 T) at 117 mum isotropic resolution revealed a continuous pattern of anterograde labeling from the habenula via the fasciculus retroflexus to the interpeduncular nucleus. Alternatively, the less invasive systemic administration of MnCl2 allowed for monitoring of the dynamic uptake pattern of respective neural components with even higher reproducibility across animals. Time courses covered the range from 42 min to 24 h after injection. In conclusion, manganese-enhanced MRI may open new ways for functional assessments of the habenulo-interpeduncular system in animal models with cognitive impairment.

Animals↗

PubMed1988

Antagonistic interactions between alleles of the RpII215 locus in Drosophila melanogaster.

The RpII215 locus encodes the large subunit of RNA polymerase II (polII). Three of 22 RpII215 alleles cause a synergistic enhancement of the mutant phenotype elicited by mutations in the Ultrabithorax (Ubx) locus. We have recovered and analyzed three new mutations that suppress this enhancement. All three mutations map to the RpII215 locus. In addition to suppressing the Ubx enhancement of other RpII215 alleles, two of the new mutations, JH1 and WJK2, themselves enhance Ubx. RpII215 alleles can be placed into three classes based on their ability to enhance Ubx. Class I alleles, including Ubl, C4, C11, JH1, and WJK2, enhance Ubx when heterozygous with class II alleles, which include wild-type RpII215. Class III alleles, which include amorphic alleles, do not enhance Ubx. The third new mutation, WJK1, is a conditional amorphic allele, which behaves like a class III allele at 29 degrees but like a class II allele at 19 degrees. Another mutant phenotype is caused by certain RpII215 alleles, including all class I alleles. This phenotype is a synergistic enhancement of a mutant phenotype elicited by mutations at the Delta (Dl) locus. Unlike the enhancement of Ubx, the enhancement of Dl is not dependent upon antagonistic interactions between different classes of RpII215 alleles.

Alleles↗

PubMed1994

The analeptic effect of methamphetamine in pentobarbital-narcotized rats is mediated via a dopaminergic-cholinergic mechanism.

Methamphetamine (MAP) administered in doses of 0.5 to 5 mg/kg i.p. to rats anesthetized with pentobarbital produced a shortening of the duration of loss of righting reflex. This analeptic effect of MAP was blocked by atropine but not by atropine methylbromide, indicating the central cholinergic nature of the response. This effect was also blocked by the D1 and D2 dopamine antagonists SCH 23390 (0.2 mg/kg) and raclopride (2 mg/kg), respectively. Pentobarbital decreased sodium-dependent high-affinity choline uptake (HACU) in frontal cortex and hippocampus as measured in synaptosomes from treated rats. MAP given to pentobarbital-narcotized rats restored HACU activity to nonanesthetized levels, but this restorative effect of MAP was blocked by SCH 23390 or raclopride. These data suggest that in addition to a cholinergic mechanism, the analeptic effect of MAP involves the dopamine system. alpha-Methyl-p-tyrosine, but not reserpine, pretreatment completely blocked the MAP analeptic response. In reserpinzed rats, MAP produced a markedly enhanced analeptic response. Studies of the effects of repeated administration of MAP on its analeptic activity were also undertaken in view of the well known sensitization to the locomotor and stereotypic effects of the amphetamines that occur with repeated intermittent administration. Rats pretreated daily with MAP (5 mg/kg) for 5 or 12 days showed neither tolerance nor sensitization to the analeptic effect of subsequent MAP administrations. 3H-quinuclidinyl benzilate-binding studies also showed no changes in muscarinic binding characteristics of membranes prepared from cortex or hippocampus of rats pretreated chronically with MAP. These and our earlier studies suggest that the analeptic effect of MAP is mediated via a dopaminergic-cholinergic mechanism.

Animals↗

PubMed2000

Pitfalls in homozygosity mapping.

There is much interest in use of identity-by-descent (IBD) methods to map genes, both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid means of mapping autosomal recessive genes in consanguineous families by identifying chromosomal regions that show homozygous IBD segments in pooled samples. In this report, we point out some potential pitfalls that arose during the course of homozygosity mapping of the enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so that the region containing the disease locus was missed as a result of pooling; (2) identification of a homozygous IBD region unrelated to the disease locus; and (3) the potential for inflation of LOD scores as a result of underestimation of the extent of inbreeding, which Broman and Weber suggest may be quite common.

Alleles↗

PubMed1996

Is irregular regression of corpora lutea in climacteric women caused by age-induced alterations in the "tissue control system"?

PROBLEM: We have recently observed that the regression of corpora lutea (CL) in women during the reproductive period of life is accompanied by a diminution of Thy-1 differentiation protein release from vascular pericytes and an accumulation of T lymphocytes and activated macrophages among both degenerating granulosa lutein cells (GLC) and theca lutein cells. These data suggest that the immune system and other stromal factors, representing components of the "tissue control system," may play a role in regression of the CL. We investigated degenerating CL from climacteric women to address the possibility that the decline of immune functions with advancing age may result in incomplete regression of luteal tissue. This could contribute to the altered hormonal profiles and abnormal uterine bleeding that frequently occur during the climacteric. METHOD: Immunoperoxidase staining and image analysis were used to localize Thy-1 differentiation protein of vascular pericytes, cytokeratin staining of GLC, neural cell adhesion molecule expression by theca lutein cells, CD15 of neutrophils, CD4, CD14, CD68, and leukocyte common antigens of macrophages, and CD3 and CD8 determinants of T lymphocytes. We also investigated the expression of luteinizing hormone receptor (LH receptor) and mitogen activated protein kinases (MAP kinases) in luteal cells. Samples of regressing luteal tissue were obtained during the follicular phase from perimenopausal women (age 45-50) who exhibited prolonged or irregular cycles. For comparison, luteal tissues from women with regular cycles (age 29-45) and CL of pregnancy were also investigated. RESULTS: Corpora lutea of the climacteric women exhibited irregular regression of luteal tissue characterized by a lack of cytoplasmic vacuolization and nuclear pyknosis in GLC, and by a persistence of theca lutein cells exhibiting hyperplasia and adjacent theca externa layers. This was accompanied by a continuing release of Thy-1 differentiation protein from vascular pericytes. Persisting GLC lacked surface expression of macrophage markers (CD4, CD14, CD68 and leukocyte common antigen) as well as nuclear granules exhibiting CD15 of neutrophils, detected in regularly regressing GLC. In addition, such persisting GLC showed weak or no LH receptor expression, and retained the expression of cytokeratin. They also exhibited enhanced staining for MAP kinases. Strong cytoplasmic MAP kinase expression with occasional nuclear translocation was also detected in persisting theca lutein cells, indicating high metabolic activity of these cells. T lymphocytes, although occasionally present in luteal stroma within luteal convolutions, did not invade among persisting GLC and were virtually absent from layers of theca externa and theca lutein cells. CONCLUSIONS: These data indicate that the regressing CL in climacteric women may exhibit persistence of luteal cells, perhaps because of age-induced alterations of the immune system and other local stromal homeostatic mechanisms involved in the elimination of luteal cells. Persisting GLC and/or theca lutein cells may exhibit abnormal hormonal secretion that contributes to the alteration of target tissues, such as the endometrium, resulting in abnormal uterine bleeding, hyperplasia, and neoplasia.

Adult↗

PubMed2004

Ictal SPECT analysis in epilepsy: subtraction and statistical parametric mapping techniques.

Seizures are associated with an increase in regional cerebral blood flow (rCBF). In partial seizures the increased blood flow closely corresponds with the site of seizure origin. Using tracers that accumulate and remain "fixed" in different areas of the brain proportional to rCBF at the time of injection, ictal SPECT is now an important tool for localization of seizures in a presurgical evaluation. However, the best methods for interpretation of partial seizure-induced changes in rCBF remain unclear. Numerous computer-aided tools have been used to increase objectivity and accuracy of ictal SPECT analysis. This review examines the uses of ictal-interictal subtraction methods and statistical parametric mapping (SPM) to enhance interpretation and utility of ictal SPECT. The review covers the evolution of advanced ictal SPECT imaging analysis techniques and the authors' clinical experience with the use of subtraction and SPM methods. The authors discuss the impact of ictal SPECT subtraction or difference imaging methods and the initial evidence for proof-of-principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with temporal and extratemporal lobe epilepsy. The limitations of both methodologies are discussed, and suggestions for further study of validation, improvement, and routine clinical implementation of advanced analysis methods are provided.

Algorithms↗